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Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylation
Joint modeling of a number of phenotypes using multivariate methods has often been neglected in genome-wide association studies and if used, replication has not been sought. Modern omics technologies allow characterization of functional phenomena using a large number of related phenotype measures, w...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587582/ https://www.ncbi.nlm.nih.gov/pubmed/28878392 http://dx.doi.org/10.1038/s41467-017-00453-3 |
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author | Shen, Xia Klarić, Lucija Sharapov, Sodbo Mangino, Massimo Ning, Zheng Wu, Di Trbojević-Akmačić, Irena Pučić-Baković, Maja Rudan, Igor Polašek, Ozren Hayward, Caroline Spector, Timothy D. Wilson, James F. Lauc, Gordan Aulchenko, Yurii S. |
author_facet | Shen, Xia Klarić, Lucija Sharapov, Sodbo Mangino, Massimo Ning, Zheng Wu, Di Trbojević-Akmačić, Irena Pučić-Baković, Maja Rudan, Igor Polašek, Ozren Hayward, Caroline Spector, Timothy D. Wilson, James F. Lauc, Gordan Aulchenko, Yurii S. |
author_sort | Shen, Xia |
collection | PubMed |
description | Joint modeling of a number of phenotypes using multivariate methods has often been neglected in genome-wide association studies and if used, replication has not been sought. Modern omics technologies allow characterization of functional phenomena using a large number of related phenotype measures, which can benefit from such joint analysis. Here, we report a multivariate genome-wide association studies of 23 immunoglobulin G (IgG) N-glycosylation phenotypes. In the discovery cohort, our multi-phenotype method uncovers ten genome-wide significant loci, of which five are novel (IGH, ELL2, HLA-B-C, AZI1, FUT6-FUT3). We convincingly replicate all novel loci via multivariate tests. We show that IgG N-glycosylation loci are strongly enriched for genes expressed in the immune system, in particular antibody-producing cells and B lymphocytes. We empirically demonstrate the efficacy of multivariate methods to discover novel, reproducible pleiotropic effects. |
format | Online Article Text |
id | pubmed-5587582 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55875822017-09-08 Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylation Shen, Xia Klarić, Lucija Sharapov, Sodbo Mangino, Massimo Ning, Zheng Wu, Di Trbojević-Akmačić, Irena Pučić-Baković, Maja Rudan, Igor Polašek, Ozren Hayward, Caroline Spector, Timothy D. Wilson, James F. Lauc, Gordan Aulchenko, Yurii S. Nat Commun Article Joint modeling of a number of phenotypes using multivariate methods has often been neglected in genome-wide association studies and if used, replication has not been sought. Modern omics technologies allow characterization of functional phenomena using a large number of related phenotype measures, which can benefit from such joint analysis. Here, we report a multivariate genome-wide association studies of 23 immunoglobulin G (IgG) N-glycosylation phenotypes. In the discovery cohort, our multi-phenotype method uncovers ten genome-wide significant loci, of which five are novel (IGH, ELL2, HLA-B-C, AZI1, FUT6-FUT3). We convincingly replicate all novel loci via multivariate tests. We show that IgG N-glycosylation loci are strongly enriched for genes expressed in the immune system, in particular antibody-producing cells and B lymphocytes. We empirically demonstrate the efficacy of multivariate methods to discover novel, reproducible pleiotropic effects. Nature Publishing Group UK 2017-09-06 /pmc/articles/PMC5587582/ /pubmed/28878392 http://dx.doi.org/10.1038/s41467-017-00453-3 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Shen, Xia Klarić, Lucija Sharapov, Sodbo Mangino, Massimo Ning, Zheng Wu, Di Trbojević-Akmačić, Irena Pučić-Baković, Maja Rudan, Igor Polašek, Ozren Hayward, Caroline Spector, Timothy D. Wilson, James F. Lauc, Gordan Aulchenko, Yurii S. Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylation |
title | Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylation |
title_full | Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylation |
title_fullStr | Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylation |
title_full_unstemmed | Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylation |
title_short | Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylation |
title_sort | multivariate discovery and replication of five novel loci associated with immunoglobulin g n-glycosylation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587582/ https://www.ncbi.nlm.nih.gov/pubmed/28878392 http://dx.doi.org/10.1038/s41467-017-00453-3 |
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